Diabetes is known to adversely affect the circulatory system of the retina. This usually occurs in several stages, two of which are background diabetic retinopathy and proliferative diabetic retinopathy. In the proliferative stage of diabetic retinopathy, poor circulation in the retina causes it to become oxygen-deprived (causing ischemia of the retinal and choroidal tissues). In response to this oxygen deprivation, neovascularization occurs, wherein vessels develop in an attempt to maintain sufficient oxygen in the retina. However, the newly-formed vessels are delicate and hemorrhage easily, leaking blood into the vitreous, thereby causing decreased vision. In latter stages of the disease, subsequent vessel growth and scar tissue can cause retinal detachment and glaucoma.
It is well-known that there is a close correlation between the onset of diabetic retinopathy and loss of oxygen in the retina. See, for example, O. P. Van Bijsterveld (Editor), Diabetic Retinopathy, Martin Dunitz Ltd., London, (2000); N. D. Wangsa-Wirawan and R. A. Linsenmeier, “Retinal Oxygen: Fundamental and Clinical Aspects,” Arch. Opthalmol. 121, 547-557 (2003); B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, and M. Prakash. “Subnormal Retinal Oxygenation Response Precedes Diabetic-like Retinopathy,” Invest. Opthalmol. Vis. Sci. 40, 2100-2105 (1999), and R. Roberts, W. Zhang, Y. Ito, and B. A. Berkowitz, “Spatial Pattern and Temporal Evolution of Retinal Oxygenation Response in Oxygen-Induced Retinopathy,” Invest. Opthalmol. Vis. Sci. 44, 5315-5320 (2003).
Choroidal neovascularization has also been attributed to choroidal ischemias (Choroidal Neovascularization Correlated With Choroidal. Ischemia, Ann-Pascale Guagnini, MD; Bernadette Snyers, MD; Alexandra Kozyreff, MD; Laurent Levecq, MD; Patrick De Potter, MD, PhD Arch Opthalmol. (2006) 124:1063). Choroidal neovascularization can occur in the setting of age-related macular degeneration and is the leading cause of blindness in the age group of 65 years and older in the western countries.
Several patents disclose the use of compounds and pharmaceutical formulations for treating retinopathy or ocular ischemia. For example, U.S. Pat. No. 7,064,141 discloses a method for preventing, treating or inhibiting development of simple retinopathy and preproliferative retinopathy by use of a pharmaceutical composition having angiotensin II antagonistic activity. U.S. Pat. No. 6,943,145 discloses compounds and a method for the prevention and treatment of diabetic retinopathy. U.S. Pat. No. 6,916,824 discloses methods of treating cataracts and diabetic retinopathy with tricyclic pyrones. U.S. Pat. No. 6,156,785 discloses a method for increasing oxygen tension in the optic nerve and retina by administration of carbonic anhydrase inhibitors. U.S. Pat. No. 5,919,813 discloses the use of a protein tyrosine kinase pathway inhibitor in the treatment of diabetic retinopathy.
U.S. Pat. No. 7,074,307 discloses electrochemical sensors for the measurement of analytes in biological fluids. The patent discloses the production of oxygen by an electrode in order to allow the electrochemical sensor to function at sufficient oxygen levels independent of the oxygen concentrations in the surrounding environment.
U.S. Pat. No. 5,855,570 discloses an oxygen-producing bandage. The invention is a portable, self-contained device for the topical application of oxygen to promote the healing of skin wounds. The device includes a wound dressing that incorporates electrochemical, chemical, or thermal means for generating high purity oxygen. The device can regulate the supply of oxygen to an area above the wound at various concentrations, pressures and dosages. The device is driven by a built-in or accessory power source. Ambient air is brought into contact with a gas permeable cathode. Oxygen present in the air is reduced at the cathode to negative ions (i.e. peroxide, superoxide or hydroxyl ions) and/or their unprotonated and protonated neutral species. One or more of these species diffuse through an electrolyte and are then oxidized at a gas permeable anode to produce a high concentration of oxygen directly above the wound.
U.S. Pat. No. 4,795,423 discloses oxygenated perfluorinated perfusion of the ocular globe to treat ischemic retinopathy. The ocular globe is penetrated with two small cannulae and an inflow and outflow perfusion is established with an oxygenated perfluorochemical emulsion or other physiologically compatible oxygenated liquid at a rate and for a duration, sufficient to permit the natural healing process to occur.
However, there remains a need for precisely and controllably treating ischemic and pre-ischemic conditions in mammals. It would be particularly advantageous to treat such conditions without introducing chemicals into the biological tissue. There is a particular need for precisely and controllably treating ischemic and pre-ischemic conditions in such a manner in the eye, as commonly found in patients suffering from diabetic retinopathy.